Influence of a β‐Alkoxy Substituent on the CH Activation Chemistry of Alkyl Ethers

Abstract

C À H activation reactions of 1,2-dimethoxyethane and methyl tert-butyl ether with methyl aryldiazoacetates or styryldiazoacetate catalyzed by Rh 2 (S-DOSP) 4 result in the formation of 2-aryl-or 2-styryl-substituted propanoic acids with asymmetric induction up to 95% ee.

Catalytic asymmetric C–H insertion reactions of α-diazocarbonyl compounds

“…Lower reaction temperatures were found to favour increased enantioselectivity. 64,163,164 Improvements in both yields and enantioselectivity were noted upon changing from an electron-donating (X = OMe) to an electron-withdrawing (X = Cl) aromatic substituent for aryl diazoacetate precursors, 67,163,165,166 as had previously been noted in intramolecular C-H insertion studies. 93,107 As seen in Scheme 16, insertion is favoured at positions α to oxygen, 62,167,168 with the same preference also holding true for insertion adjacent to nitrogen, 63,65,124,164,169,170 and at benzylic 64,171 and allylic 20,[172][173][174] sites.…”

“…166 No C-H insertion is observed at the methyl group adjacent to oxygen in 1-methoxy-4-methylbenzene 123 [Scheme 18(b)], due to probable delocalisation of the electron lone pairs of oxygen into the benzene ring. 163 The p-methoxy group in this reaction serves the function of sterically protecting the ring from possible cyclopropanation, as was observed for the reaction of methyl p-bromophenyldiazoacetate and toluene.…”

“…8,18 Thus, insertion into secondary C-H bonds is generally favoured for intermolecular diazo decomposition, as this represents the best balance between electronic and steric effects ( Figure 19). 124,166,167,171 …”

Functionalization of Carbon–Hydrogen Bonds Through Transition Metal Carbenoid Insertion

“…Davies and coworkers found, however, quite the opposite to be true for the b position [101]. In an attempt to access rapidly chiral crown ethers through asymmetric C-H insertion, they were surprised to discover that 18-crown-6 130 failed to react with diazo ester 79 in the presence of Rh 2 (S-DOSP) 4 to form any insertion product, even adjacent to the activating oxygen atom (Scheme 30, left).…”

Late-stage C–H functionalization of complex alkaloids and drug molecules via intermolecular rhodium-carbenoid insertion

“…Therefore, we chose to explore the reactions of alkaloids containing N-methyl groups. Functionalization of electronically activated methyl C-H bonds has been observed, but only a few examples of C-H insertion into methyl C-H bonds in the presence of activated methylene and/or methine C-H bonds have been reported 42,[47][48][49] , and none of those feature a basic amine. We found for alkaloids possessing an N-Me functionality, the most favoured product in each case arose from C-H insertion into the said N-methyl group (Fig.…”